Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more ...comparable groups.
From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible for both radical prostatectomy (RP) and external beam radiotherapy (EBRT). Brachytherapy (BT) was a third option for some. Health-related quality of life was measured by expanded prostate cancer index composite (EPIC) up to 12 months after treatment.
In the sexual domain, RP led to worse summary scores (P<0.001) and more often to a clinically relevant deterioration from baseline than BT and EBRT (79%, 33%, 34%, respectively). In the urinary domain, RP also led to worse summary scores (P=0.014), and more deterioration from baseline (41%, 12%, 19%, respectively). Only on the irritative/obstructive urinary scale, more BT patients (40%) showed a relevant deterioration than RP (17%) and EBRT patients (11%). In the bowel domain, the treatment effects did not differ.
This study provides a more unbiased comparison of treatment effects, as men were more comparable at baseline. Our results suggest that, for quality of life, radiotherapy is as least as good an option as RP for treating localised prostate cancer.
Purpose
To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy.
Methods
In ...15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate–rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V
75Gy
) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2–3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated.
Results
A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate–rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V
75Gy
of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings.
Conclusions
Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall.
Structured :
Authors – Hollister SJ, Lin CY, Saito E, Lin CY, Schek RD, Taboas JM, Williams JM, Partee B, Flanagan CL, Diggs A, Wilke EN, Van Lenthe GH, Müller R, Wirtz T, Das S, Feinberg SE, ...Krebsbach PH
Objective – To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction.
Experimental Variable – Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy.
Outcome Measure – Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro‐CT scanning, mechanical testing and histology.
Setting – Departments of Biomedical Engineering, Oral/Maxillofacial Surgery, and Oral Medicine, Pathology and Oncology at the University of Michigan.
Results – Results showed that the design/fabrication approach could create scaffolds with designed porous architecture to match craniofacial anatomy. These scaffolds could be fabricated from a wide range of biomaterials, including titanium, degradable polymers, and degradable calcium phosphate ceramics. Mechanical tests showed that fabricated scaffolds had compressive modulus ranging 50 to 2900 MPa and compressive strength ranging from 2 to over 56 MPa, within the range of human craniofacial trabecular bone. In vivo testing of designed scaffolds showed that they could support bone regeneration via delivery of BMP‐7 transduced human gingival fibroblasts in a mouse model. Designed hydroxyapatite scaffolds with pore diameters ranging from 400 to 1200 microns were implanted in minipig mandibular defects for 6 and 18 weeks. Results showed substantial bone ingrowth (between 40 and 50% at 6 weeks, between 70 and 80% at 18 weeks) for all scaffolds, with no significant difference based on pore diameter.
Conclusion – Integrated image‐based design and solid free‐form fabrication can create scaffolds that attain desired elasticity and permeability while fitting any 3D craniofacial defect. The scaffolds could be manufactured from degradable polymers, calcium phosphate ceramics and titanium. The designed scaffolds supported significant bone regeneration for all pore sizes ranging from 300 to 1200 microns. These results suggest that designed scaffolds are clinically applicable for complex craniofacial reconstruction.
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic ...interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.
Background Late anorectal toxicity is a frequent adverse event of external beam radiotherapy (EBRT) for prostate cancer. The pathophysiology of anorectal toxicity remains unknown, but we speculate ...that rectal distensibility is impaired due to fibrosis. Our goal was to determine whether EBRT induces changes of rectal distensibility as measured by an electronic barostat and to explore whether anorectal complaints are related to specific changes of anorectal function.
Methods Thirty‐two men, irradiated for localized prostate carcinoma, underwent barostat measurements, anorectal manometry, and completed a questionnaire prior to and 1 year after radiotherapy. The primary outcome measure was rectal distensibility in response to stepwise isobaric distensions. In addition, we assessed sensory thresholds, anal pressures, and anorectal complaints.
Key Results External beam radiotherapy reduced maximal rectal capacity (227 ± 14 mL vs 277 ± 15 mL; P < 0.001), area under the pressure‐volume curve (3212 ± 352 mL mmHg vs 3969 ± 413 mL mmHg; P < 0.005), and rectal compliance (15.7 ± 1.2 mL mmHg−1vs 17.6 ± 0.9 mL mmHg−1; P = 0.12). Sensory pressure thresholds did not significantly change. Sixteen of the 32 patients (50%) had one or more anorectal complaints. Patients with urgency (n = 10) had a more reduced anal squeeze and maximum pressure (decrease 29 ± 11 mmHg vs 1 ± 7 mmHg; P < 0.05 and 31 ± 12 mmHg vs 2 ± 8 mmHg; P < 0.05 respectively) compared with patients without complaints, indicating a deteriorated external anal sphincter function.
Conclusions & Inferences Irradiation for prostate cancer leads to reduced rectal distensibility. In patients with urgency symptoms, anal sphincter function was also impaired.
Background
Recent developments in esophageal cancer treatment, including studies exploring active surveillance following chemoradiotherapy, have led to a need for clear terminology and definitions ...regarding different multimodal treatment options.
Objective
The aim of this study was to reach worldwide consensus on the definitions and semantics of multimodal esophageal cancer treatment.
Methods
In total, 72 experts working in the field of multimodal esophageal cancer treatment were invited to participate in this Delphi study. The study comprised three Delphi surveys sent out by email and one online meeting. Input for the Delphi survey consisted of terminology obtained from a systematic literature search. Participants were asked to respond to open questions and to indicate whether they agreed or disagreed with different statements. Consensus was reached when there was ≥75% agreement among respondents.
Results
Forty-nine of 72 invited experts (68.1%) participated in the first online Delphi survey, 45 (62.5%) in the second survey, 21 (46.7%) of 45 in the online meeting, and 39 (86.7%) of 45 in the final survey. Consensus on neoadjuvant and definitive chemoradiotherapy with or without surgery was reached for 27 of 31 items (87%). No consensus was reached on follow-up after treatment with definitive chemoradiotherapy.
Conclusion(s)
Consensus was reached on most statements regarding terminology and definitions of multimodal esophageal cancer treatment. Implementing uniform criteria facilitates comparison of studies and promotes international research collaborations.
•The properties of LiFePO4 with different binders (PVdF, PAA, PMMA) were examined.•LiFePO4 with PMMA binder shows the best electrochemical properties.•The apparent diffusion coefficient of LiFePO4 ...with PMMA is 9.13×10−11cm2s−1.•The apparent diffusion coefficient of LiFePO4 with PAA is 2.57×10−11cm2s−1.
Impacts of different polymer binders (PVdF, PAA and PMMA) on electrochemical performance of the LiFePO4 cathode in Li-ion batteries are investigated. From CV result, the voltage between redox peaks of the LiFePO4 with PVdF, PAA and PMMA binders are 0.26, 0.20 and 0.23V, respectively. The current of the LiFePO4 with PMMA binder shows the highest value of 1.4mA. The apparent diffusion coefficient of the LiFePO4 with PVdF, PAA and PMMA binders is 8.30×10−12, 2.57×10−11 and 9.13×10−11cm2s−1, respectively. The discharge capacities of the LiFePO4 with PVdF, PAA and PMMA binders are 106, 143 and 154mAhg−1 at an initial cycle, respectively. FE-SEM studies clearly demonstrate that plate-like PAA and PMMA coating on the electrodes form a protective film, which may decrease the amount of the deposits, thus decreasing crack and crystallization on the electrode surface. Achieved results indicate that PVdF, PAA and PMMA binders show better properties than the traditional one, especially PMMA one.
Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic ...testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3′ AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future.
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